5P12-RANTES / Orion Biotech - LARVOL DELTA

Study of OB-002 in Patients With Refractory Metastatic Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Orion Biotechnology Polska Sp. z o.o. | Phase classification: P1b ➔ P1 | N=36 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Monotherapy • Phase classification • Trial withdrawal • Breast Cancer • Colorectal Cancer • Gastric Cancer • Genito-urinary Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. (PubMed, PLoS One) - "Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model."

Journal • Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Study of OB-002 in Patients With Refractory Metastatic Cancer (clinicaltrials.gov) - P1b | N=36 | Not yet recruiting | Sponsor: Orion Biotechnology Polska Sp. z o.o.

Metastases • Monotherapy • New P1 trial • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

[VIRTUAL] Orion Biotechnology (BIO 2021) - "Orion’s breakthrough science and novel approach is led by a proprietary drug discovery platform that unlocks the discovery of analogs through efficient exploration of the GPCR-drug interface, allowing for the precision engineering of peptide and protein ligands to produce highly potent novel drug candidates with user-defined signaling profiles. The company is growing a multi-asset high-value portfolio of drug candidates with significant clinical potential, led by Orion’s first best-in-class analog, OB-002."

Oncology

Evaluation of the Safety, Acceptability, and Pharmacokinetic Profile of a Gel Formulation of OB-002 in Healthy Volunteers. (PubMed, AIDS Res Hum Retroviruses) - "OB-002 is an extremely potent CCR5 antagonist that has previously been shown to completely block transmission in a non-human primate model of HIV infection. Overall, the product had a positive acceptability profile, and most study participants would consider using the product for protection against HIV or pregnancy. Future studies are needed to assess the extended safety and acceptability of OB-002H gel in sexually active participants."

Clinical • Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

[VIRTUAL] Phase 1 evaluation of the safety, acceptability, and pharmacokinetic profile of an OB-002H gel (HIVR4P 2021) - "BACKGROUND: OB-002 is an extremely potent CCR5 antagonist that has previously been shown to completely block vaginal transmission of a SHIV virus (SF162P3) in a non-human primate model of HIV infection (Veazey R et al. OB-002H gel was safe and well tolerated with a good acceptability profile and high intentionality of future use. Future studies are needed to assess the extended safety and acceptability of the product in sexually active participants."

Clinical • Late-breaking abstract • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Arrestin recruitment to CCR5: potent CCL5 analogs reveal differences in dependence on receptor phosphorylation and isoform-specific recruitment bias. (PubMed, Mol Pharmacol) - "5P12-RANTES does not elicit receptor phosphorylation or arrestin recruitment...Highly potent chemokine analog inhibitors act via the modulation of receptor desensitization, a process initiated by the recruitment of arrestin proteins. This study shows that potent CCL5 analogs differ from each other and from the parent chemokine in the extent and quality of CCR5-arrestin association that they elicit, providing valuable insights into CCR5 pharmacology and cell biology that will facilitate the development of new medicines targeting this important receptor."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Oncology

Orion Biotechnology Receives Funding to Test OB-002 for Treatment of COVID-19 (GlobeNewswire) - "Orion Biotechnology Canada Ltd....today announced that it is receiving advisory services and conditional funding from the National Research Council Industrial Research Assistance Program (NRC IRAP), to support the development of Orion’s lead compound, OB-002, a promising treatment for SARS-CoV-2 infection associated acute respiratory distress syndrome (ARDS). OB-002 is the first of a new class of drugs, called Chemokine Analogs..."

Cytokine storm • Financing • Infectious Disease • Novel Coronavirus Disease

"#OB002 Significantly Reduces Bone Metastasis in a Murine Model of #BreastCancer https://t.co/cyyGlVNZIc" (@1stOncology)

Preclinical

OB-002 significantly reduces bone metastasis in a murine model of breast cancer (PRNewswire) - "Orion Biotechnology Canada, Ltd...announced that OB-002 was able to significantly reduce bone metastasis in a murine model of breast cancer...Female BALB/c mice received orthotopic implantation of 4T1-M3_Luc cells into the mammary fat pad....The mice randomized to receive OB-002 at a dose of 20 mg/kg demonstrated a significant reduction in Day 20 primary tumor volume compared to placebo and the mice randomized to receive 80 mg/kg had a significant reduction in spinal bone metastasis."

Preclinical

OB-002 (5P12-RANTES) is significantly more potent than other CCR5 antagonists in development for the treatment or prevention of HIV infection (IAS-HIV 2019) - "In the same assay, PRO 140 (Leronlimab), a CCR5 monoclonal antibody that is currently in development for a HIV treatment indication (Thompson Curr Opin HIV AIDS 2018), gave a potency (5.6 nM) 28-fold lower than that of OB-002. The difference in performance between OB-002 and maraviroc in NHP models could be due to the superior potency of OB-002, which according to our results is the most potent CCR5 inhibitor currently in development for HIV indications. These data further support development of OB-002 as a highly potent candidate microbicide for HIV prevention. Phase 1 rectal and vaginal safety studies are planned to start in Q3 2019."